a study to learn about the study medicine (called pf-07220060 in combination with pf-07104091) in participants with breast cancer and solid tumors

Conditions: Breast Cancer; Solid Tumors

Summary: the purpose of this clinical trial is to learn about the safety and effects of the study medicine (called pf-07220060 and pf-07104091) in people with breast cancer. this clinical study consists of 2 parts (part 1 and part 2). in part 1, we are seeking participants who: * have been diagnosed with breast cancer (bc) of either types: * have hr+, her2- bc * refractory hr-positive/her2-positive bc * have other solid tumors other than bc in part 2, we are seeking participants who: -have hr-positive/her2-negative bc part 1 will include increasing doses of pf-07220060 with pf-07104091. in part 2, participants will take 1 of 2 study medicine combinations. this will help us decide the highest amount of study medicines that can be safety given to people. all participants in this study will receive pf-07220060 with pf-07104091 by mouth. we will compare participant experiences to help us determine if pf-07220060 with pf-07104091 is safe and effective. participants will take part in this study for about 2 years. during this time, they will receive the study medicine, an x-ray imaging, and will be observed for safety and effects of the study medicines.


Eligibility criteria:
inclusion criteria * part 1: breast cancer (bc) * hr+, her2- bc * refractory hr-positive/her2-positive bc * part 1: solid tumors other than bc * part 2: * hr-positive/her2-negative bc * lesion: * part 1: evaluable lesion (including skin or bone lesion only) * part 2: measurable lesion per recist v1.1 * prior systemic treatment * part 1: hr-positive/her2-negative bc * at least 1 line of soc, including cdk4/6 inhibitor therapy and endocrine therapy, for advanced or metastatic disease. * prior chemotherapy in the metastatic setting is allowed. * part 1: hr-positive/her2-positive bc * at least 1 prior treatment of approved her2 targeting therapy. * part 1: solid tumors other than bc * participants with no standard therapy available or for which no local regulatory approved standard therapy is available that would confer significant clinical benefit in the medical judgement of the investigator. * part 2a: at least 1 prior systemic therapy for advanced or metastatic disease, including cdk4/6 inhibitor treatment and et. * parts 2b: at least 1 prior endocrine therapy for advanced or metastatic disease. progression during treatment or within 12 months of completion of adjuvant endocrine therapy is acceptable. * part 2b: up to 1 prior line of chemotherapy for advanced/metastatic disease is allowed. * general inclusion criteria * eastern cooperative oncology group (ecog) performance status (ps) 0 or 1 * adequate renal, liver, and bone marrow function * resolved acute effects of any prior therapy to baseline severity exclusion criteria: * all study parts: permanent treatment discontinuation from prior cdk 4 and/or cdk2 inhibitor due to treatment related toxicity. * part 2b and 1c: prior treatment with any cdk 4/6 inhibitor, or serds (e.g. fulvestrant), or everolimus, or any agent whose mechanism of action is to inhibit the pi3k-mtor pathway for advanced disease. * parts 2b and 2c: prior treatment with any cdk4/6 inhibitor for advanced disease. * parts 2b and 2c: prior treatment with an investigational endocrine therapy for advanced disease. * part 2c: prior neoadjuvant or adjuvant treatment with a nonsteroidal aromatase inhibitor ai (ie, anastrozole or letrozole) with disease recurrence while on or within 12 months of completing treatment. * part 2c: any prior systemic treatment for advanced disease. * prior irradiation to \>25% of the bone marrow * current use of drugs which have a risk for qtc prolongation * current use or anticipated need for food or drugs that are known strong cyp3a4/5, strong ugt2b7 or ugt1a9 inhibitors or inducers * participation in other studies involving investigational drug(s) within 4 weeks prior to study entry * participants with any other active malignancy within 3 years prior to enrollment except for adequately treated basal cell or squamous cell skin cancer, or carcinoma in situ of the cervix, bowen's disease * major surgery within 4 weeks prior to study entry * radiation therapy within 4 weeks prior to study entry. * clinically important hypertension * known or suspected hypersensitivity to pf-07220060, pf-07104091, letrozole, fulvestrant, or goserelin (or equivalent to induce chemical menopause if applicable) * known abnormalities in coagulation. anticoagulation with subcutaneous heparin or prophylactic doses of anticoagulant are allowed * known active uncontrolled or symptomatic central nervous system (cns) metastases * active inflammatory gi disease * current use or anticipated need for proton pump inhibitors (ppi) within 14 days prior to first dose of the study intervention * previous high-dose chemotherapy requiring stem cell rescue * participants with active, uncontrolled bacterial, fungal, or viral infection, including hepatitis b virus (hbv), hepatitis c virus (hcv), and known human immunodeficiency virus (hiv) or acquired immunodeficiency syndrome (aids) related illness * other protocol specific exclusion criteria may apply

Keywords: cyclin-dependent kinase 2 (cdk2) cyclin-dependent kinase 4 (cdk4) estrogen receptor-positive/human epidermal growth factor receptor 2 negative (er+/her2-) estrogen receptor-positive/refractory hormone receptor positive (er+/her2+) hormone receptor positive/human epidermal growth factor receptor 2 negative (hr+/her2-)